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Estimation of human percutaneous uptake for two novel brominated flame retardants, 2-ethylhexyl tetrabromobenzoate (TBB) and bis(2-ethylhexyl) tetrabromophthalate (TBPH) using the parallelogram method
Citation:
Knudsen, G., M. Hughes, J. Sanders, AND L. Birnbaum. Estimation of human percutaneous uptake for two novel brominated flame retardants, 2-ethylhexyl tetrabromobenzoate (TBB) and bis(2-ethylhexyl) tetrabromophthalate (TBPH) using the parallelogram method. Society of Toxicology, New Orleans, LA, March 13 - 17, 2016.
Impact/Purpose:
Experiments using the parallelogram approach to estimate human systemic absorption to the brominated flame retardants 2-ethylhexyl tetrabromobenzoate (TBB) and bis(2-ethylhexyl) tetrabromophthalate (TBPH) suggest the compound is bioavailable. Based on the data approximately 7% of dermally applied TBB and 2% of TBPH may be bioavailable to humans.
Description:
2-ethylhexyl- tetrabromobenzoate (TBB) and bis(2-ethylhexyl)-tetrabromobenzoate (TBPH) are novel brominated flame retardants (FRs). TBPH is used as a plasticizer or with TBB in polyurethane foam FRs. TBB & TBPH have been detected in both indoor and outdoor environmental samples. In the present study, a parallelogram approach was used predict internal dose for exposed humans. Human or rat skin samples received 100 nmol of TBB or TBPH/cm2. [14C]-radioactivity was determined in dosed skin and media (in vitro) or excreta, tissues, and skin (in vivo). For TBB, human skin and media contained an average of 12% and 0.2% of the total dose, respectively, while the rat skin and media contained 36% and 2%, respectively. In vivo, 10% of the dose was in dosed skin, while 13% reached systemic circulation by 24 hours. HPLC analyses of perfusate found TBB was completely converted to tetrabrombenzoic acid. TBPH was poorly absorbed, with <0.01% of the in vitro dose recovered in perfusate. In vivo, dosed skin contained 8% of applied TBPH and 1.2% was recovered in excreta and tissues. It is clear that TBB can be absorbed and metabolized to tetrabromobenzoic acid by the skin and dermal contact with TBB may represent an important route of exposure. Together, these in vitro data in human and rat skin and in vivo data from rats may be used to predict absorption in humans following dermal exposure to TBB or TBPH. Based on these data, approx. 7% of dermally applied TBB and 2% of TBPH may be bioavailable to humans. (This abstract does not represent U.S. EPA policy.)